Case of the Month

Edited by Robert N. Johnson, MD

Case #115, Jan, 2019

Presented by:

Joseph Alsberge, MD

A 39-year-old man with blurred vision in both eyes

Figure 1: Color photograph of the right nerve and macula. Note the cystic changes in the macula.

Figure 2: Color photograph of the left nerve and macula. Note the cystic changes in the macula.

Case History

A 39-year-old man presented for evaluation of longstanding decreased vision in both eyes. On examination, visual acuity was 20/80 in the right eye and 20/63 in the left eye. The anterior segment examination was unremarkable. Dilated examination revealed a spokewheel pattern of folds radiating out from the fovea in both eyes (Figures 1 and 2). The periphery was normal in both eyes (Figures 3 and 4). Fluorescein angiography revealed subtle irregular foveal fluorescence with no late leakage in either eye (Figures 5 and 6). Optical coherence tomography revealed cystic cavities and retinal pigment epithelial changes in both eyes (Figures 7-10).

Figure 3: Wide-field color photograph of the right eye. Note the normal peripheral retina.

Figure 4: Wide-field color photograph of the left eye. Note the normal peripheral retina.

Figure 5: Wide-field fluorescein angiogram of the right eye. Note the mild irregular flourescence in the macula outling the plicate appearance in the fovea.

Figure 6: Wide-field fluorescein angiogram of the left eye. Note the mild irregular flourescence in the macula outling the plicate appearance in the fovea as seen in the right eye.

Figure 7: SD-OCT of the right macula. Note the prominent cystic spaces, primarily in the middle layers of the retina.

Figure 8: SD-OCT of the left macula. Note the prominent cystic spaces, primarily in the middle layers of the retina.

Figure 9: Enface SD-OCT of the right macula. Note the prominent cystic spaces.

Figure 10: Enface SD-OCT of the left macula. Note the prominent cystic spaces.

What is your Diagnosis?

Differential Diagnosis

Cystoid macular edema (secondary to diabetes, retinal vascular occlusion, uveitis, or retinitis pigmentosa), taxane drug-associated maculopathy, nicotinic acid maculopathy, X-linked retinoschisis, Goldmann-Favre Syndrome, stellate non-hereditary idiopathic foveomacular retinoschisis, myopic foveoschisis, vitreomacular traction syndrome.

 

Additional History and Diagnosis

Given the absence of late leakage on angiography, cystoid macular edema could be ruled out. The patient had no past medical history and was not taking any systemic medicines. He had no family history of similar eye disease. Electroretinography was performed and revealed reduced A- and B-wave amplitudes, but without an alteration in the B to A ratio. Genetic testing revealed a mutation in the RS1 gene located on the X chromosome, confirming the diagnosis of X-linked retinoschsis.

 

Discussion

X-linked retinoschisis (XLRS) is retinal degenerative disease that is characterized by cystic maculopathy and peripheral schisis. It is the most common form of juvenile onset retinal degeneration in males.1

The disease is caused by mutations in the RS1 gene located on the X chromosome, which encodes retinoschisin, a protein complex that plays a role in cell-to-cell adhesion in the retina.1 In males, the RS1 mutation is completely penetrant (meaning all male individuals with the mutation will develop disease), although there is considerable variation in the severity of disease.2 Female carriers who are heterozygous for the RS1 mutation typically have no clinical findings, but those who are homozygous have similar ocular findings as males.3

Foveal schisis is the characteristic diagnostic feature of XLRS. It typically has a “spokewheel” pattern, as demonstrated in the case presented here, and does not leak on fluorescein angiography. In adulthood, the schisis may disappear and be replaced with atrophic retinal pigment epithelial changes.2 Peripheral retinoschisis, which occurs in the superficial retinal layers, is also noted in 50% of patients, and is often located in the inferotemporal quadrant.1 Holes in the inner layer of the peripheral schisis cavity lead to the formation of so-called “vitreous veils”. Peripheral white-yellow dendriform lesions, representing occluded retinal vessels, may also develop (see, for example, Case of the Month September, 2012: http://westcoastretina.com/sept-2012.html). Vision threatening complications include retinal detachment and vitreous hemorrhage.

Classically, XLRS is associated with a so-called “negative electroretinogram”. This refers to the scenario where the A-wave amplitude exceeds the B-wave amplitude while recording a bright light stimulus during scotopic testing conditions. However, as demonstrated in the case presented here, not all patients with XLRS have a negative electroretinogram.4

Take Home Points

  • X-linked retinoschisis (XLRS) is characterized by foveal schisis, often in a spokewheel pattern, and peripheral schisis, which may lead to vitreous hemorrhage or retinal detachment.
  • XLRS is caused by mutations in the RS1 gene, which encodes retinoschisin, a retinal adhesion protein.
  • Classically, patients with XLRS have a “negative electroretinogram”, but this is not always the case.

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References

  1. Tang S, Ding X, Luo Y. Hereditary Vitreoretinal Degenerations. In: Ryan SJ, Schachat AP, Sadda SR, eds. Retina. Fifth ed. Elsevier:836-851.
  2. Agarwal A. Heredodystrophic Disorders Affecting the Pigment Epithelium and Retina. In: Agarwal, A. Gass’ Atlas of Macular Diseases. Fifth ed. Elsevier:239-436.
  3. Rodriguez FJ, Rodriguez A, Mendoza-Londono, et al. X-linked retinoschisis in three females from the same family: a phenotype-genotype correlation. Retina 2005;25:69-74.
  4. Renner AB, Kellner U, Fiebig B, et al. ERG variability in X-linked congenital retinoschisis patients with mutations in the RS1 gene and the diagnostic importance of fundus autofluorescence and OCT. Doc Ophthalmol 2008;116:97-109.

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